Mesenchymal stem cell-derived exosomes carrying miR-486-5p inhibit glycolysis and cell stemness in colorectal cancer by targeting NEK2.

IF 3.4 2区 医学 Q2 ONCOLOGY BMC Cancer Pub Date : 2024-11-06 DOI:10.1186/s12885-024-13086-9
Facai Cui, Yu Chen, Xiaoyu Wu, Weifeng Zhao
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Abstract

Colorectal cancer (CRC) is a major global concern. Mesenchymal stem cell-derived exosomes (MSC-EXOs) have demonstrated efficacy as a therapeutic approach for colorectal cancer. However, the precise mechanism by which MSC-EXOs treat colorectal cancer remains unclear. Human umbilical cord (hUC)-MSC-EXOs were isolated and identified. Cell Counting Kit-8 (CCK-8), Transwell, and colony formation assays were used to assess the activity of CRC cells. Glucose consumption, lactic acid production, and extracellular acidification rate (ECAR) were measured to assess glycolytic activity. Cell stemness was assessed using a sphere-formation assay. Furthermore, MSC-exosomal microRNAs (miRNAs) in CRC tissues were analyzed using the EVmiRNA database, and aberrantly expressed miRNAs in CRC cells were obtained from the Gene Expression Omnibus (GEO) database. The binding relationship between miR-486-5p and the never in mitosis gene A-related kinase 2 (NEK2) was predicted using the Starbase database and validated through RNA binding protein immunoprecipitation (RIP) and dual luciferase assays. These results showed that hUC-MSC-EXOs inhibited the proliferation and metastasis of CRC cells. Moreover, glycolysis and stemness abilities of CRC cells also decreased after treatment with hUC-MSC-EXOs. miR-486-5p was found to be enriched in hUC-MSC-EXOs and significantly downregulated in CRC cells. miR-486-5p directly bound to NEK2. Overexpression of NEK2 reversed the inhibitory effect of miR-486-5p on CRC cell glycolysis and stemness. Our study highlights that hUC-MSC-EXO miR-486-5p inhibits glycolysis and cell stemness in CRC by targeting NEK2. This finding offers compelling evidence supporting the potential application of hUC-MSC-EXOs in the treatment of CRC.

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间充质干细胞衍生的外泌体携带miR-486-5p,通过靶向NEK2抑制结直肠癌中的糖酵解和细胞干性。
结直肠癌(CRC)是全球关注的一大问题。间充质干细胞衍生外泌体(MSC-EXOs)作为一种结直肠癌治疗方法已被证明具有疗效。然而,间充质干细胞外泌体治疗结直肠癌的确切机制仍不清楚。我们分离并鉴定了人脐带(hUC)-间充质干细胞-EXOs。使用细胞计数试剂盒-8(CCK-8)、Transwell和集落形成试验评估CRC细胞的活性。测量葡萄糖消耗、乳酸生成和细胞外酸化率(ECAR)以评估糖酵解活性。细胞干性通过球形成试验进行评估。此外,还利用 EVmiRNA 数据库分析了 CRC 组织中的间充质干细胞外微RNA(miRNA),并从基因表达总库(GEO)数据库中获得了 CRC 细胞中异常表达的 miRNA。利用Starbase数据库预测了miR-486-5p与从未有丝分裂基因A相关激酶2(NEK2)之间的结合关系,并通过RNA结合蛋白免疫沉淀(RIP)和双荧光素酶测定进行了验证。这些结果表明,hUC-间充质干细胞-EXOs抑制了CRC细胞的增殖和转移。miR-486-5p直接与NEK2结合。过表达 NEK2 逆转了 miR-486-5p 对 CRC 细胞糖酵解和干性的抑制作用。我们的研究表明,hUC-MSC-EXO miR-486-5p通过靶向NEK2抑制了CRC细胞的糖酵解和细胞干性。 这一发现为hUC-MSC-EXO在治疗CRC方面的潜在应用提供了有力的证据。
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来源期刊
BMC Cancer
BMC Cancer 医学-肿瘤学
CiteScore
6.00
自引率
2.60%
发文量
1204
审稿时长
6.8 months
期刊介绍: BMC Cancer is an open access, peer-reviewed journal that considers articles on all aspects of cancer research, including the pathophysiology, prevention, diagnosis and treatment of cancers. The journal welcomes submissions concerning molecular and cellular biology, genetics, epidemiology, and clinical trials.
期刊最新文献
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